The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Deficiency of the Microglial Receptor CX3CR1 Impairs Postnatal Functional Development of Thalamocortical Synapses in the Barrel Cortex
Open accessAbstract
Accumulative evidence indicates that microglial cells influence the normal development of brain synapses. Yet, the mechanisms by which these immune cells target maturating synapses and influence their functional development at early postnatal stages remain poorly understood. Here, we analyzed the role of CX3CR1, a microglial receptor activated by the neuronal chemokine CX3CL1 (or fractalkine) which controls key functions of microglial cells. In the whisker-related barrel field of the mouse somatosensory cortex, we show that the recruitment of microglia to the sites where developing thalamocortical synapses are concentrated (i.e., the barrel centers) occurs only after postnatal day 5 and is controlled by the fractalkine/CX3CR1 signaling pathway. Indeed, at this developmental stage fractalkine is overexpressed within the barrels and CX3CR1 deficiency delays microglial cell recruitment into the barrel centers. Functional analysis of thalamocortical synapses shows that CX3CR1 deficiency also delays the functional maturation of postsynaptic glutamate receptors which normally occurs at these synapses between the first and second postnatal week. These results show that reciprocal interactions between neurons and microglial cells control the functional maturation of cortical synapses.
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“KO mice lacking fractalkine receptor show transient excitatory hyperconnectivity followed by weak synaptic multiplicity and reduced functional brain connectivity in adulthood11,12, suggesting that a failure to eliminate synapses at the correct developmental time prevents the normal strengthening of synaptic connections.”
From Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction (2018) · cites this paper as [12]
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Cites
Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., et al. (2011) · Science · doi:10.1126/science.1202529 · Cited by 4,244
Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.026 · Cited by 4,089 · cited 1×
“…be that MGCs, once inside TCA clusters, could contribute to the selection of synapses with a mature signature of their glutamate receptors (Yashiro and Philpot, 2008) by pruning immature synapses through phagocytosis (Paolicelli et al., 2011) in a complement-dependent manner (Schafer et al., 2012).”
BackgroundMicroglia: Active sensor and versatile effector cells in the normal and pathologic brain
Hanisch, U.-K., & Kettenmann, H. (2007) · Nature Neuroscience · doi:10.1038/nn1997 · Cited by 3,676 · cited 1×
“In the diseased adult CNS, several signaling pathways control the recruitment of microglia at sites of compromised homeostasis (Hanisch and Kettenmann, 2007; Ransohoff and Perry, 2009).”
BackgroundJung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.4106-4114.2000 · Cited by 2,632 · cited 3×
“In few experiments heterozygous CX3CR1 /eGFP mice of either sex were obtained by crossing CX3CR1 eGFP/eGFP (Jung et al., 2000) with wild-type C57BL/6J mice (Janvier).”
BackgroundMethodInfluentialNeurotrophins and their receptors: A convergence point for many signalling pathways
Chao, M. V. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1078 · Cited by 2,298
Microglial physiology: unique stimuli, specialized responses
Ransohoff, R. M., & Perry, V. H. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132528 · Cited by 1,858 · cited 1×
“In the diseased adult CNS, several signaling pathways control the recruitment of microglia at sites of compromised homeostasis (Hanisch and Kettenmann, 2007; Ransohoff and Perry, 2009).”
BackgroundControl of microglial neurotoxicity by the fractalkine receptor
Cardona, A. E., Pioro, E. P., Sasse, M. E., Kostenko, V., Cardona, S. M., Dijkstra, I. M., Huang, D., Kidd, G., Dombrowski, S., Dutta, R., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1715 · Cited by 1,531 · cited 1×
“This chemokine is expressed by neurons; its receptor CX3CR1 is only expressed by MGCs and controls their migration and functions (Harrison et al., 1998; Maciejewski-Lenoir et al., 1999; Cardona et al., 2006; Ruitenberg et al., 2008; Liang et al., 2009; Paolicelli et al., 2011).”
BackgroundControl of Synaptic Strength by Glial TNFα
Beattie, E. C., Stellwagen, D., Morishita, W., Bresnahan, J. C., Ha, B. K., Von Zastrow, M., Beattie, M. S., & Malenka, R. C. (2002) · Science · doi:10.1126/science.1067859 · Cited by 1,344
Harrison, J. K., Jiang, Y., Chen, S., Xia, Y., Maciejewski, D., McNamara, R. K., Streit, W. J., Salafranca, M. N., Adhikari, S., Thompson, D. A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.18.10896 · Cited by 1,176 · cited 3×
“…local role of fractalkine in which cellular elements localized within the barrel hollows, possibly thalamic fibers, overexpress the chemokine at P5–P7 and thus favor directed migration of microglia (Harrison et al., 1998; Maciejewski-Lenoir et al., 1999) toward maturating thalamocortical synapses.”
BackgroundResultThe Role of Microglia in the Healthy Brain: Figure 1.
Tremblay, M.-È., Stevens, B., Sierra, A., Wake, H., Bessis, A., & Nimmerjahn, A. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.4158-11.2011 · Cited by 992 · cited 1×
“In rodents, experimental evidence shows that MGCs contribute to developmentally regulated neuronal apoptosis but also to synapse pruning (Mallat et al., 2005; Pont-Lezica et al., 2011; Schlegelmilch et al., 2011; Tremblay et al., 2011).”
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Cited by
Sorted by citations
Microglia Function in the Central Nervous System During Health and Neurodegeneration
Colonna, M., & Butovsky, O. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052358 · Cited by 2,894
“CX3CR1-CX3CL1 interactions are also required for functional maturation of thalamocortical synapses (72).”
BackgroundMicroglia promote learning-dependent synapse formation through brain-derived neurotrophic factor
Parkhurst, C. N., Yang, G., Ninan, I., Savas, J. N., Yates, J. R., Lafaille, J. J., Hempstead, B. L., Littman, D. R., & Gan, W.-B. (2013) · Cell · doi:10.1016/j.cell.2013.11.030 · Cited by 2,599
“Recent work has shown that mice lackingCX3CR1 have delayed invasion of the cortical barrel fields by microglia, and a transient delay in the normally observed AMPA receptor subunit switching in thalamocortical barrel cortex synapses (Hoshiko et al., 2012).”
BackgroundMicroglia and macrophages in brain homeostasis and disease
Li, Q., & Barres, B. A. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.125 · Cited by 1,999
A polarizing question: do M1 and M2 microglia exist?
Ransohoff, R. M. (2016) · Nature Neuroscience · doi:10.1038/nn.4338 · Cited by 1,573
Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction
Weinhard, L., di Bartolomei, G., Bolasco, G., Machado, P., Schieber, N. L., Neniskyte, U., Exiga, M., Vadisiute, A., Raggioli, A., Schertel, A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03566-5 · Cited by 790
Metadata
- Authors
- Hoshiko, M., Arnoux, I., Avignone, E., Yamamoto, N., & Audinat, E.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- The University of Osaka (JP)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-10-24
- Volume
- 32
- Issue
- 43
- Pages
- 15106-15111
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6704837
- OpenAlex
- W1996055705
- Cited by
- 384
- References
- 33
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 36 · 2023: 29 · 2022: 40 · 2021: 41 · 2020: 35 · 2019: 39 · 2018: 30 · 2017: 23 · 2016: 19 · 2015: 14 · 2014: 22 · 2013: 22
- FWCI
- 9.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Uehara Memorial Foundation
- Ministry of Education, Culture, Sports, Science and Technology (23115102)
- Japan Society for the Promotion of Science (20021018)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- CX3CR1, fractalkine, microglia, synapse maturation, thalamocortical synapses, barrel cortex, postnatal development, microglial recruitment, glutamate receptors, microglia-neuron interaction, somatosensory cortex
- MeSH terms
- CX3C Chemokine Receptor 1, Age Factors, Animals, Animals, Newborn, Developmental Disabilities, Electric Stimulation, Female, Male, Mice, Inbred C57BL, Mice, Transgenic, Somatosensory Cortex, Synapses, Thalamus, Microglia, Gene Expression Regulation, Developmental, Excitatory Amino Acid Antagonists, Statistics, Nonparametric, GABA Antagonists, Excitatory Postsynaptic Potentials, Receptors, Chemokine, Green Fluorescent Proteins, Serotonin Plasma Membrane Transport Proteins, Mice, Chemokine CX3CL1, In Vitro Techniques
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